Max Planck Institute for Metabolism Research

The human brain analyses nutrient-related and hormonal signals of the body periphery and controls by hunger and saturation induction the energy homeostasis. This central nervous control is complex and until now not fully understood. Research at the Max Planck Institute for Metabolism Research (formerly: Max Planck Institute for Neurological Research) is dedicated to deciphering these most intricate neuro-circuits. The researchers use multimodal and molecular imaging to describe intact but also abnormal metabolic regulation. Once neuronal signaling pathways of the metabolism are completely understood both in healthy people and patients, new molecular therapies for diseases such as type 2 diabetes and obesity may be developed in the long run.

Coordination of food intake, locomotion and sleep is crucial for survival, its impairment is a symptom of multiple sleep and eating disorders. We found that optogenetic activation of GABA cells in the lateral hypothalamus leads to awakening from non-REM sleep and increases food intake. Further we characterized the neuronal circuit, which connects the prefrontal cortex and the lateral hypothalamus and utilizes gamma oscillations to organize function-selective firing of neurons and to promote food-seeking.

Variations in the fat mass and obesity-associated (FTO) gene are associated with obesity. The same variants of FTO affect dopamine-dependent midbrain responses and learning from negative outcomes in humans. They furthermore modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions and facilitate neural responses elicited by food cues. These findings provide evidence for FTO-specific differences in both brain structure and function in individuals, thereby contributing to a mechanistic understanding of why FTO is a predisposing factor for obesity.

Obesity, type 2 diabetes mellitus and associated dieseases are on a constant rise and not only reduce quality of life but also are putting a burden on our society. Large efforts have been put into a better understanding of the homeostatic control mechanisms involved in regulation of body weight and energy homeostasis. It is known that maternal obesity, diabetes and hyperglycemia during pregnancy results in an increased risk for the offspring to develop obesity and diabetes later in life. By performing studies in mice, scientists can gain insights into the underlying complex mechanisms.

The increase in the prevalence of obesity and the concomitant health problems are putting a burden on our modern society. Lifestyle and genetic predisposition define the individual susceptibility to gain weight. Through identifying the genetic alterations and the subsequent investigation of the affected genes/proteins – including studies in mice – scientists hope to gain insights into the complex interaction of our genome and environment to finally identify the mechanisms that may lead e.g. to weight gain.